US5780393A - Herbicidal isoxazole and isothiazole-5-carboxamides - Google Patents

Herbicidal isoxazole and isothiazole-5-carboxamides Download PDF

Info

Publication number
US5780393A
US5780393A US08/702,779 US70277996A US5780393A US 5780393 A US5780393 A US 5780393A US 70277996 A US70277996 A US 70277996A US 5780393 A US5780393 A US 5780393A
Authority
US
United States
Prior art keywords
isoxazole
amide
carboxylic acid
group
ylethyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US08/702,779
Inventor
Trevor W. Newton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Wyeth LLC
Original Assignee
American Cyanamid Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by American Cyanamid Co filed Critical American Cyanamid Co
Priority to US08/702,779 priority Critical patent/US5780393A/en
Assigned to AMERICAN HOME PRODUCTS CORPORATION reassignment AMERICAN HOME PRODUCTS CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: NEWTON, TREVOR W.
Application granted granted Critical
Publication of US5780393A publication Critical patent/US5780393A/en
Assigned to BASF AKTIENGESELLSCHAFT reassignment BASF AKTIENGESELLSCHAFT ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AMERICAN CYANAMID COMPANY
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention relates to isoxazole- and isothiazole-5-carboxylic acid amide compounds, the preparation of said compounds, herbicidal compositions containing said compounds, and a method of controlling undesired plant growth therewith.
  • N-aralkyl and N-heteroaralkyl amides of said acids have been reported to have useful pharmaceutical and agrochemical applications; for example, U.S. Pat. No. 3,912,756 describes the preparation of N-(4-carboxyalkoxy)phenylalkylenyl isoxazole-5-carboxamides as hypolipemics; and U.S. Pat. No. 5,039,694 describes the preparation and fungicidal activity of N-(substituted heterocyclyl-methyl)isoxazole-5-carboxamides.
  • said herbicidal compositions may be used to selectively control undesirable weed species in the presence of a crop, such as a cereal crop or a leguminous crop.
  • the present invention provides herbicidal isoxazole- and isothiazole-5-carboxamide compounds of formula I ##STR2## wherein X represents an oxygen or sulfur atom; W represents an optionally substituted alkyl, alkenyl, cycloalkyl, dialkylamino, aryl, heteroaryl or aralkyl group;
  • Y represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group
  • R 1 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted acyl group
  • Z represents an optionally substituted C 1 -C 4 alkylene group with the proviso that when R 1 is hydrogen and Z is methylene, then the optional substituent does not represent cyano, thiocarbamoyl or thiocarbamoylacyl;
  • R 2 represents an optionally substituted aryl or heteroaryl group with the proviso that when X represents a sulfur atom then R 2 does not represent a furyl group or a phenyl group optionally substituted with halogen and with the further proviso that when Z represents an unsubstituted methylene group, then R 2 does not represent an unsubstituted phenyl group; or
  • Crop production can be reduced by as much as 30% to 60% by the presence of persistent and pestiferous weed species.
  • Compounds which demonstrate effective control over a broad spectrum of annual and perennial monocotyledenous and dicotyledenous weeds in the presence of a crop, while commensurately demonstrating selective tolerance toward that crop, are of great interest in agricultural practice and modern pest management programs.
  • Y represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group
  • R 1 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted acyl group
  • Z represents an optionally substituted C 1 -C 4 alkylene group
  • R 2 represents an optionally substituted aryl or heteroaryl group
  • W represents an optionally substituted alkyl, cycloalkyl, alkenyl, dialkylamino, phenyl, pyridyl, furyl or thienyl group.
  • W represents a branched C 3 -C 6 alkyl group or a phenyl group which is optionally substituted with one or two substituents independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkyl. Most preferably, W represents a t-butyl group or a phenyl group.
  • Y and R 1 each represent a hydrogen atom.
  • a preferred optionally substituted alkylene group Z has the formula --CH(R 3 )--, wherein R 3 represents a hydrogen atom or an optionally substituted C 1 -C 2 alkyl group, more preferably a methyl group.
  • R 2 preferably represents either phenyl optionally substituted by 1 or 2 moieties independently selected from halogen and C 1 -C 4 alkyl, or furyl, pyridyl, thienyl or benzothienyl. More preferably, R 2 represents a phenyl or thienyl group.
  • alkyl group designates an alkyl group which may be linear or branched and may suitably contain 1 to 10, preferably 1 to 6, carbon atoms.
  • alkyl groups are methyl, ethyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, s-pentyl, neopentyl and the like.
  • an alkenyl group may suitably contain 2 to 8 carbon atoms; a cycloalkyl group may have from 3 to 8, preferably 3 to 6, carbon atoms, more preferably 5 or 6 carbon atoms.
  • an acyl group designates a carbonyl group attached to an optionally substituted alkyl, aryl or heteroaryl group and suitably contains 2 to 8 carbon atoms.
  • An aralkyl group designates an alkyl group, defined as above, substituted by an aryl group.
  • An aryl group designates an optionally substituted phenyl or naphthyl group.
  • a heteroaralkyl group designates an alkyl group, defined as above, substituted by a heteroaryl group.
  • a heteroaryl group designates a mono- or polycyclic ring system consisting of 5- or 6-membered aromatic rings containing one or more sulfur or nitrogen or oxygen atoms or combinations thereof. Any or all of the constituent groups may be optionally substituted.
  • the optional substituent groups may be any of those customarily employed in the development of pesticidal compounds, or the modification of such compounds to influence their structure/activity, persistence, penetration or other property.
  • an optionally substituted aryl or heteroaryl group including aryl and heteroaryl parts of aralkyl, heteroaralkyl and acyl groups, may include halogen, especially fluorine, chlorine and bromine atoms, nitro, cyano, amino, hydroxyl, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, especially CF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy groups and the like.
  • the compounds of the invention may be oils, gums, or, predominantly, crystalline solid materials. Said compounds demonstrate valuable herbicidal properties and may be used in agriculture or related fields for the control of a wide spectrum of undesired monocotyledenous and dicotyledenous plant species. Further, compounds of formula I demonstrate good herbicidal activity within a wide concentration range and advantageously, may be used in crop production, such as cereal crop production or leguminous crop production without causing an unacceptable phytotoxic effect on said crops.
  • the present invention also provides a process for the preparation of a compound of formula I which comprises reacting a compound of formula II ##STR4## wherein W, X and Y are as defined hereinabove for formula I and L represents a leaving group, with a compound of formula III ##STR5## wherein Z, R 1 and R 2 are as defined hereinabove for formula I.
  • the leaving group L designates a halogen atom, such as chlorine; an acyloxy group, such as acetoxy; an alkoxy group, such as a methoxy or ethoxy group; or an aryloxy group, such as a phenoxy group.
  • L represents a methoxy or ethoxy group.
  • the reaction may be carried out in an organic solvent, for example ethanol or toluene, and at a temperature range at about room temperature to the reflux temperature of the reaction mixture.
  • the reaction is most effectively carried out under basic conditions.
  • the basic conditions may be provided by employing an excess of the amine of formula III in the reaction, for example a two-fold excess.
  • the basic conditions may be provided by the separate inclusion of a base in the reaction mixture.
  • the base may be any of those commonly employed in organic chemistry, for instance, a hydroxide, hydride, alkoxide, carbonate or hydrogen carbonate salt of an alkali metal or an alkaline earth metal; or an amine.
  • a preferable base is a tertiary amine, for example triethylamine.
  • a compound of formula I may be prepared by reacting a compound of formula II with a salt of formula IV ##STR6## wherein Z, R 1 and R 2 are as defined hereinabove and B - is a suitable anion, for example a chloride, bromide, iodide, sulfate or (R)-2-hydroxysuccinate, in the presence of a base.
  • the reaction may be carried out in an organic solvent, for example ethanol or toluene, and at a temperature range of about room temperature to the reflux temperature of the reaction mixture.
  • the base may be any of those commonly employed in organic chemistry, for instance, a hydroxide, hydride, alkoxide, carbonate or hydrogen carbonate salt of an alkali metal or an alkaline earth metal; or an amine, preferably a tertiary amine, for example triethylamine.
  • the amount of base used may be an excess amount, for example a four-fold excess.
  • the amines of formula III and the salts of formula IV are known, or may be obtained from known materials by standard synthetic techniques.
  • the formula I compounds of the invention are highly effective herbicidal agents. Accordingly, the invention further provides a herbicidal composition comprising a compound of formula I as defined above in association with at least one carrier Preferably there are at least two carriers, at least one of which is a surface-active agent.
  • a carrier as intended for use in a composition of the invention, is any material with which the active ingredient is formulated to facilitate application, or to facilitate storage, transport or handling.
  • a carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid. Any of the carriers normally used in formulating herbicidal compositions may be used.
  • Compositions according to the invention may contain about 0.5% to 95% by weight of active ingredient.
  • Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminum silicates, for example attapulgites and vermiculites; aluminum silicates, for example kaolinites, montmorillonites and micas; calcium carbonate; calcium sulfate; ammonium sulfate; synthetic hydrated silicon oxides and synthetic calcium or aluminum silicates; elements, for example carbon and sulfur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes; and solid fertilizers, for example superphosphates; and the like.
  • natural and synthetic clays and silicates for example natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminum silicates, for example attapulgites and vermiculites; aluminum silicates
  • Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons, for example benzene, toluene and xylene; petroleum fractions, for example kerosene and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene and trichloroethane; and the like or mixtures thereof.
  • Agricultural compositions may be formulated and transported in a concentrated form and subsequently diluted before application.
  • a carrier which is a surface-active agent facilitates this process of dilution.
  • at least one carrier in a composition according to the invention is a surface-active agent.
  • the composition may contain at least two carriers, at least one of which is a surface active agent.
  • a surface-active agent may be an emulsifying agent, a dispersing agent or a wetting agent; it may be nonionic or ionic.
  • suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulfonic acids; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide or propylene oxide; fatty acid esters of glycerol, sorbitan, sucrose or pentaerythritol; condensates of these with ethylene oxide or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylcresol, with ethylene oxide or propylene oxide; sulfates or sulfonates of these condensation products; alkali or alkaline earth metal salts, preferably sodium salts, or sulfuric or sulfonic acid esters containing
  • compositions of the invention may take the form of wettable powders, dusts, granules, soluble granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates, microemulsions or the like.
  • Aqueous dispersions, emulsions, solutions and such compositions obtained by diluting a wettable powder or a concentrate according to the invention with water, are also included within the scope of the invention.
  • composition of the invention may also contain other active ingredients, such as other compounds possessing herbicidal, insecticidal or fungicidal properties.
  • the present invention further provides a method for the control of undesirable monocotyledenous and dicotyledenous annual, perennial and aquatic plant species which comprises applying to the foliage of said plant species or to the soil or water containing seeds or other propagating organs thereof a herbicidally effective amount of an isoxazole- or isothiazole-5-carboxamide compound of formula I.
  • Dosage rates for effective weed control may vary according to the prevailing conditions such as soil conditions, weather conditions, weed population and density, mode of application and the like. Dosage rates of about 0.01 kg/ha to 10 kg/ha, preferably about 0.05 kg/ha to 4.0 kg/ha offer effective weed control.
  • NMR nuclear magnetic resonance
  • flash chromatography refers to column chromatography performed under moderate pressure.
  • Hexabutyl distannoxane (16.0 mL, 31.5 mmol) is added dropwise, with cooling, to a stirred solution of ethyl propionate (13.7 mL, 126 mmol) and trimethylacetaldoximoyl chloride (8.5 g, 63 mmol, prepared according to J. N. Kim et al, J. Org. Chem., 57, 6649, 1992) in dry toluene.
  • the mixture is stirred at room temperature for 16 h and the solvent is evaporated in vacuo.
  • the organic extracts are combined, dried over magnesium sulfate and concentrated in vacuo.
  • the optical purity of the sample of free amine so generated is determined by NMR spectroscopy using a chiral shift reagent, e.g. Eu(fod) 3 .
  • the bulk of the salt is then recrystallized from water and the optical purity of the amine portion of the salt is redetermined by the same procedure. This process is repeated until a satisfactory optical purity is achieved. If the salt is allowed to recrystallize slowly, a ratio of 92:8 of the S-enantiomer to the R-enantiomer of the amine can be obtained after a single recrystallization.
  • the yield of (S)-1-(thien-2-ylethyl)ammonium (R)-2-hydroxysuccinate is 195.0 g, 50% of theory, mp>300° C.
  • Triethylamine (3.26 g, 32 mmol) is added to a stirred suspension of (S)-1-(thien-2-ylethyl)ammonium (R)-2-hydroxysuccinate (2.30 g, 8.8 mmol) in absolute ethanol (25 mL), and the mixture is stirred at room temperature for 5 min, during which time a clear solution is formed.
  • Ethyl 3-t-butyl-isoxazole-5-carboxylate (1.58 g, 8 mmol) is added and the mixture is refluxed for 9 days.
  • a further small portion of triethylamine is added to the reaction mixture, and the mixture is heated at reflux temperature for another 8 h. The solvent is evaporated in vacuo to give a residue.
  • Chlorocarbonyl sulfenyl chloride (11.24 g, 86 mmol) is added dropwise to a stirred suspension of 2-fluorobenzamide (10.80 g, 78 mmol) in dry toluene.
  • the mixture is heated gradually over a period of 30 minutes to a temperature of about 80° C. (a clear solution is formed with evolution of gas), stirred for approximately 1 h at 80° C., heated to about 98° C., stirred at 98° C. for 5 h, and distilled to remove the toluene and excess chlorocarbonyl sulfenyl chloride.
  • the resultant residue is purified by flash column chromatography (silica gel, toluene) to give ethyl 3-(2-fluorophenyl)isothiazole-5-carboxylate (1.0 g, 40%) as yellow crystals, mp 53°-54° C., plus ethyl 3-(2-fluorophenyl)isothiazole-4-carboxylate (0.8 g, 32%) as a yellow oil.
  • the preemergence tests are conducted by spraying a liquid formulation of the test compound onto the soil in which the seeds of the plant species have recently been sown.
  • the postemergence tests are conducted by spraying a liquid formulation of the test compound onto seedling plants.
  • the soil used in the tests is a prepared horticultural loam.
  • the formulations used in the tests are prepared from solutions of the test compound in acetone containing 0.4% by weight of an alkylphenol/ethylene oxide condensate. These acetone solutions are diluted with water and the resulting formulations applied at dosage levels corresponding to 0.8 kg of active material per hectare in a volume equivalent to 900 liters per hectare.
  • the herbicidal effect of the test compounds is evaluated twenty days after treatment and is recorded on a 0-9 scale. A rating of 0 indicates growth equivalent to the untreated control, a rating of 9 indicates complete death.

Abstract

There are provided isoxazole- and isothiazole-5-carboxamide compounds of formula I <IMAGE> (I) which are useful for the control of undesirable monocotyledenous and dicotyledenous plant species in the presence of crops such as cereal and leguminous crops. Also provided are herbicidal compositions and methods of using same.

Description

This application claims the benefit of copending prior U.S. Provisional Application Ser. No. 60/002,728 filed on Aug. 24, 1995.
BACKGROUND OF THE INVENTION
This invention relates to isoxazole- and isothiazole-5-carboxylic acid amide compounds, the preparation of said compounds, herbicidal compositions containing said compounds, and a method of controlling undesired plant growth therewith.
Amides of isoxazole- and isothiazole-5-carboxylic acids are well known in the chemical literature. Several N-aralkyl and N-heteroaralkyl amides of said acids have been reported to have useful pharmaceutical and agrochemical applications; for example, U.S. Pat. No. 3,912,756 describes the preparation of N-(4-carboxyalkoxy)phenylalkylenyl isoxazole-5-carboxamides as hypolipemics; and U.S. Pat. No. 5,039,694 describes the preparation and fungicidal activity of N-(substituted heterocyclyl-methyl)isoxazole-5-carboxamides.
Further, the herbicidal activity of isoxazole-5-carboxamides which are substituted in the 4-position by a carbonyl or carboxyl group is described in U.S. Pat. No. 5,080,708 and U.S. Pat. No. 5,201,932. In U.S. Pat. No. 5,080,708, the benzyl amide of a 3-alkyl-isoxazole-5-carboxylic acid, which is unsubstituted in the 4-position, is cited as an intermediate in the preparation of herbicidal compounds. However, there is no indication that said compound, lacking a 4-substituent, may show herbicidal activity.
Therefore, it is an object of this invention to provide herbicidal isoxazole- and isothiazole-5-carboxamide compounds.
It is another object of this invention to provide herbicidal compositions and methods utilizing said heterocyclyl-5-carboxamide compounds.
It is a feature of this invention that said herbicidal compositions may be used to selectively control undesirable weed species in the presence of a crop, such as a cereal crop or a leguminous crop.
These and other objects and features of the invention will become apparent from the detailed description set forth below.
SUMMARY OF THE INVENTION
The present invention provides herbicidal isoxazole- and isothiazole-5-carboxamide compounds of formula I ##STR2## wherein X represents an oxygen or sulfur atom; W represents an optionally substituted alkyl, alkenyl, cycloalkyl, dialkylamino, aryl, heteroaryl or aralkyl group;
Y represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group;
R1 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted acyl group;
Z represents an optionally substituted C1 -C4 alkylene group with the proviso that when R1 is hydrogen and Z is methylene, then the optional substituent does not represent cyano, thiocarbamoyl or thiocarbamoylacyl; and
R2 represents an optionally substituted aryl or heteroaryl group with the proviso that when X represents a sulfur atom then R2 does not represent a furyl group or a phenyl group optionally substituted with halogen and with the further proviso that when Z represents an unsubstituted methylene group, then R2 does not represent an unsubstituted phenyl group; or
the N-oxides thereof; or
the optical isomers thereof.
There are further provided methods for the control of undesirable monocotyledenous and dicotyledenous plant species in the presence of a crop, such as a cereal crop or leguminous crop. Herbicidal compositions and methods of using same are also provided.
DETAILED DESCRIPTION OF THE INVENTION
Crop production can be reduced by as much as 30% to 60% by the presence of persistent and pestiferous weed species. Compounds which demonstrate effective control over a broad spectrum of annual and perennial monocotyledenous and dicotyledenous weeds in the presence of a crop, while commensurately demonstrating selective tolerance toward that crop, are of great interest in agricultural practice and modern pest management programs.
It has now been found that a broad spectrum of grass weeds and broad-leafed weeds may be effectively controlled in the presence of a crop, such as a cereal crop or leguminous crop, with little or no phytotoxic injury to said crop by the preemergence or postemergence application of an isoxazole- or isothiazole-5-carboxamide compound of formula I ##STR3## wherein X represents an oxygen or sulfur atom; W represents an optionally substituted alkyl, alkenyl, cycloalkyl, dialkylamino, aryl, heteroaryl or aralkyl group;
Y represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group;
R1 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted acyl group;
Z represents an optionally substituted C1 -C4 alkylene group; and
R2 represents an optionally substituted aryl or heteroaryl group; or
the N-oxides thereof; or
the optical isomers thereof.
Preferably, W represents an optionally substituted alkyl, cycloalkyl, alkenyl, dialkylamino, phenyl, pyridyl, furyl or thienyl group.
More preferably, W represents a branched C3 -C6 alkyl group or a phenyl group which is optionally substituted with one or two substituents independently selected from halogen, C1 -C4 alkyl, C1 -C4 alkoxy or C1 -C4 haloalkyl. Most preferably, W represents a t-butyl group or a phenyl group.
Preferably, Y and R1 each represent a hydrogen atom.
A preferred optionally substituted alkylene group Z has the formula --CH(R3)--, wherein R3 represents a hydrogen atom or an optionally substituted C1 -C2 alkyl group, more preferably a methyl group.
The group R2 preferably represents either phenyl optionally substituted by 1 or 2 moieties independently selected from halogen and C1 -C4 alkyl, or furyl, pyridyl, thienyl or benzothienyl. More preferably, R2 represents a phenyl or thienyl group.
In the specification and claims the term alkyl group designates an alkyl group which may be linear or branched and may suitably contain 1 to 10, preferably 1 to 6, carbon atoms. Examples of such alkyl groups are methyl, ethyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, s-pentyl, neopentyl and the like. Similarly, an alkenyl group may suitably contain 2 to 8 carbon atoms; a cycloalkyl group may have from 3 to 8, preferably 3 to 6, carbon atoms, more preferably 5 or 6 carbon atoms. The term, an acyl group, as used in the specification and claims designates a carbonyl group attached to an optionally substituted alkyl, aryl or heteroaryl group and suitably contains 2 to 8 carbon atoms.
An aralkyl group designates an alkyl group, defined as above, substituted by an aryl group. An aryl group designates an optionally substituted phenyl or naphthyl group. A heteroaralkyl group designates an alkyl group, defined as above, substituted by a heteroaryl group. A heteroaryl group designates a mono- or polycyclic ring system consisting of 5- or 6-membered aromatic rings containing one or more sulfur or nitrogen or oxygen atoms or combinations thereof. Any or all of the constituent groups may be optionally substituted.
The optional substituent groups may be any of those customarily employed in the development of pesticidal compounds, or the modification of such compounds to influence their structure/activity, persistence, penetration or other property. Optional substituent groups designated above in the terms: an optionally substituted alkyl, alkenyl or cycloalkyl group, including the alkyl portions of aralkyl, heteroaralkyl or acyl groups, include halogen, especially fluorine, chlorine or bromine atoms, phenyl, nitro, cyano, hydroxyl, C1 -C4 alkoxy, C1 -C4 alkyl, C1 -C4 haloalkoxy, (C1 -C4 alkoxy)- carbonyl, amino, alkyl- and phenyl-sulfinyl, -sulphenyl and -sulfonyl groups, mono- and di(C1-C4alkyl)amino groups and the like, preferably halogen.
Optional substituent groups defined above in the terms: an optionally substituted aryl or heteroaryl group, including aryl and heteroaryl parts of aralkyl, heteroaralkyl and acyl groups, may include halogen, especially fluorine, chlorine and bromine atoms, nitro, cyano, amino, hydroxyl, C1 -C4 alkyl, C1 -C4 haloalkyl, especially CF3, C1 -C4 alkoxy, C1 -C4 haloalkoxy groups and the like.
Included in the scope of the present invention are all possible enantiomers and diastereoisomers of the compounds of the formula I having one or more optically active centers, and also the N-oxides of the isoxazole or isothiazole ring nitrogen atom.
Particularly interesting herbicidal activity has been found in the (S)-isomers of those formula I compounds wherein Z represents the group --*CH(R3)--, and *C designates an asymetric center.
Among the specific compounds of the invention which may be represented by formula I are compounds such as:
(S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-phenylethyl)amide;
(S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(2-Fluorophenyl)isothiazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(S)-3-Phenyl-isoxazole-5-carboxylic acid (1-phenylethyl)amide;
(R/S)-3-Phenyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-Styryl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-Cyclohexyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-Dimethylamino-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(2'-Pyridyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(2'-Thienyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(4'-Methylphenyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(4'-Methoxyphenyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(2',4'-Difluorophenyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-Benzyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-Butyl-4-chloro-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-Butyl-4-methyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid N-methyl,N-(1-thien-2-ylethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid N-acetyl,N-(1-thien-2-ylethyl)amide;
3-t-Butyl-isoxazole-5-carboxylic acid (thien-2-yl-methyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-(4'-chlorophenyl)ethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-(4'-methylphenyl)ethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-furan-2-ylethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-(2'-pyridyl)ethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-thien-3-ylethyl)amide;
(R/S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-(2'-benzothienyl)ethyl)amide and the like.
The compounds of the invention may be oils, gums, or, predominantly, crystalline solid materials. Said compounds demonstrate valuable herbicidal properties and may be used in agriculture or related fields for the control of a wide spectrum of undesired monocotyledenous and dicotyledenous plant species. Further, compounds of formula I demonstrate good herbicidal activity within a wide concentration range and advantageously, may be used in crop production, such as cereal crop production or leguminous crop production without causing an unacceptable phytotoxic effect on said crops.
The present invention also provides a process for the preparation of a compound of formula I which comprises reacting a compound of formula II ##STR4## wherein W, X and Y are as defined hereinabove for formula I and L represents a leaving group, with a compound of formula III ##STR5## wherein Z, R1 and R2 are as defined hereinabove for formula I.
The leaving group L as used in the specification and claims designates a halogen atom, such as chlorine; an acyloxy group, such as acetoxy; an alkoxy group, such as a methoxy or ethoxy group; or an aryloxy group, such as a phenoxy group. Preferably, L represents a methoxy or ethoxy group.
When L represents an alkoxy group, the reaction may be carried out in an organic solvent, for example ethanol or toluene, and at a temperature range at about room temperature to the reflux temperature of the reaction mixture. The reaction is most effectively carried out under basic conditions. The basic conditions may be provided by employing an excess of the amine of formula III in the reaction, for example a two-fold excess.
Alternatively, the basic conditions may be provided by the separate inclusion of a base in the reaction mixture. The base may be any of those commonly employed in organic chemistry, for instance, a hydroxide, hydride, alkoxide, carbonate or hydrogen carbonate salt of an alkali metal or an alkaline earth metal; or an amine. A preferable base is a tertiary amine, for example triethylamine.
In another embodiment of the above process, a compound of formula I may be prepared by reacting a compound of formula II with a salt of formula IV ##STR6## wherein Z, R1 and R2 are as defined hereinabove and B- is a suitable anion, for example a chloride, bromide, iodide, sulfate or (R)-2-hydroxysuccinate, in the presence of a base. The reaction may be carried out in an organic solvent, for example ethanol or toluene, and at a temperature range of about room temperature to the reflux temperature of the reaction mixture. The base may be any of those commonly employed in organic chemistry, for instance, a hydroxide, hydride, alkoxide, carbonate or hydrogen carbonate salt of an alkali metal or an alkaline earth metal; or an amine, preferably a tertiary amine, for example triethylamine. The amount of base used may be an excess amount, for example a four-fold excess.
Many starting isoxazole- and isothiazole-5-carboxylates of formula II wherein L represents an alkoxy group are known or may be prepared by known methods, such as those described by O. Moriya et al, J. Chem. Soc., Chem. Comm., 17, (1991); R. Howe et al, J. Chem. Soc., Chem. Comm., 524, (1973), or D. Buffel et al, J. Org. Chem., 49, 2165, (1984).
The amines of formula III and the salts of formula IV are known, or may be obtained from known materials by standard synthetic techniques.
The formula I compounds of the invention are highly effective herbicidal agents. Accordingly, the invention further provides a herbicidal composition comprising a compound of formula I as defined above in association with at least one carrier Preferably there are at least two carriers, at least one of which is a surface-active agent.
A carrier, as intended for use in a composition of the invention, is any material with which the active ingredient is formulated to facilitate application, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid. Any of the carriers normally used in formulating herbicidal compositions may be used. Compositions according to the invention may contain about 0.5% to 95% by weight of active ingredient.
Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminum silicates, for example attapulgites and vermiculites; aluminum silicates, for example kaolinites, montmorillonites and micas; calcium carbonate; calcium sulfate; ammonium sulfate; synthetic hydrated silicon oxides and synthetic calcium or aluminum silicates; elements, for example carbon and sulfur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes; and solid fertilizers, for example superphosphates; and the like.
Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons, for example benzene, toluene and xylene; petroleum fractions, for example kerosene and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene and trichloroethane; and the like or mixtures thereof.
Agricultural compositions may be formulated and transported in a concentrated form and subsequently diluted before application. The presence of small amounts of a carrier which is a surface-active agent facilitates this process of dilution. Thus, preferably at least one carrier in a composition according to the invention is a surface-active agent. For example the composition may contain at least two carriers, at least one of which is a surface active agent.
A surface-active agent may be an emulsifying agent, a dispersing agent or a wetting agent; it may be nonionic or ionic. Examples of suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulfonic acids; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide or propylene oxide; fatty acid esters of glycerol, sorbitan, sucrose or pentaerythritol; condensates of these with ethylene oxide or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylcresol, with ethylene oxide or propylene oxide; sulfates or sulfonates of these condensation products; alkali or alkaline earth metal salts, preferably sodium salts, or sulfuric or sulfonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulfate, sodium secondary alkyl sulfates, sodium salts of sulfonated castor oil, and sodium alkaryl sulfonates such as dodecylbenzene sulfonate; polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide; and the like.
The compositions of the invention may take the form of wettable powders, dusts, granules, soluble granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates, microemulsions or the like.
Aqueous dispersions, emulsions, solutions and such compositions obtained by diluting a wettable powder or a concentrate according to the invention with water, are also included within the scope of the invention.
The composition of the invention may also contain other active ingredients, such as other compounds possessing herbicidal, insecticidal or fungicidal properties.
The present invention further provides a method for the control of undesirable monocotyledenous and dicotyledenous annual, perennial and aquatic plant species which comprises applying to the foliage of said plant species or to the soil or water containing seeds or other propagating organs thereof a herbicidally effective amount of an isoxazole- or isothiazole-5-carboxamide compound of formula I.
Particularly interesting control of grasses and broad-leafed weeds, both preemergence and postemergence, has been found. The selective control of said weeds in important crop species such as wheat, barley, maize, rice and soybeans has also been found.
Dosage rates for effective weed control may vary according to the prevailing conditions such as soil conditions, weather conditions, weed population and density, mode of application and the like. Dosage rates of about 0.01 kg/ha to 10 kg/ha, preferably about 0.05 kg/ha to 4.0 kg/ha offer effective weed control.
For a more clear understanding of the invention, specific examples thereof are set forth below. The invention described and claimed herein is not to be limited in scope by these merely illustrative examples. Indeed, various modifications of the invention in addition to those exemplified and described herein will become apparent to those skilled in the art from the following examples and the foregoing description. Such modifications are also intended to fall within the scope of the appended claims
In the examples, the term NMR designates nuclear magnetic resonance and flash chromatography refers to column chromatography performed under moderate pressure.
EXAMPLE 1 (S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-phenethyl)amide
(a) Ethyl 3-t-butyl-isoxazole-5-carboxylate
Hexabutyl distannoxane (16.0 mL, 31.5 mmol) is added dropwise, with cooling, to a stirred solution of ethyl propionate (13.7 mL, 126 mmol) and trimethylacetaldoximoyl chloride (8.5 g, 63 mmol, prepared according to J. N. Kim et al, J. Org. Chem., 57, 6649, 1992) in dry toluene. The mixture is stirred at room temperature for 16 h and the solvent is evaporated in vacuo. The resultant residue is purified by flash column chromatography (silica gel, hexane/ethyl acetate 8:1 v/v) to give ethyl 3-t-butyl-isoxazole-5-carboxylate (12 g, 97%) as a yellow oil, which is used in the following reaction.
(b) (S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-phenethyl)amide
A solution of ethyl 3-t-butyl-isoxazole-5-carboxylate (1.58 g, 8 mmol) and (S)-1-phenethylamine (2.91 g, 24 mmol) in absolute ethanol is refluxed for 7 days and concentrated in vacuo to give a residue. The residue is purified by flash column chromatography (silica gel, hexane/ethyl acetate 4:1 v/v) to give (s)-3-t-butyl-isoxazole-5-carboxylic acid (1-phenethyl)amide (1.01 g, 46%) as colorless crystals, mp 130°-131° C.
EXAMPLE 2 (S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide
(a) (S)-(1-Thien-2-ylethyl)ammonium (R)-2-hydroxysuccinate
(R/S)-1-(Thien-2-ylethyl)amine (381.6 g, 3.0 mol) is added dropwise to a stirred solution of D-(+)-2-hydroxysuccinic acid (402.3 g, 3.0 mol) in water at room temperature. During the addition, the temperature of the solution rises to 55°-60° C. The solution is allowed to stand at room temperature for about 16 h, during which time a crystalline precipitate forms and the precipitate is filtered off. The optical purity of the salt is determined as follows: A small quantity of the salt is treated with a 10% molar excess of sodium hydroxide in water and the aqueous solution is extracted with dichloromethane. The organic extracts are combined, dried over magnesium sulfate and concentrated in vacuo. The optical purity of the sample of free amine so generated is determined by NMR spectroscopy using a chiral shift reagent, e.g. Eu(fod)3. The bulk of the salt is then recrystallized from water and the optical purity of the amine portion of the salt is redetermined by the same procedure. This process is repeated until a satisfactory optical purity is achieved. If the salt is allowed to recrystallize slowly, a ratio of 92:8 of the S-enantiomer to the R-enantiomer of the amine can be obtained after a single recrystallization. The yield of (S)-1-(thien-2-ylethyl)ammonium (R)-2-hydroxysuccinate is 195.0 g, 50% of theory, mp>300° C.
(b) (S)-3-t-Butyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide
Triethylamine (3.26 g, 32 mmol) is added to a stirred suspension of (S)-1-(thien-2-ylethyl)ammonium (R)-2-hydroxysuccinate (2.30 g, 8.8 mmol) in absolute ethanol (25 mL), and the mixture is stirred at room temperature for 5 min, during which time a clear solution is formed. Ethyl 3-t-butyl-isoxazole-5-carboxylate (1.58 g, 8 mmol) is added and the mixture is refluxed for 9 days. A further small portion of triethylamine is added to the reaction mixture, and the mixture is heated at reflux temperature for another 8 h. The solvent is evaporated in vacuo to give a residue. The residue is dissolved in dichloromethane, washed with 1N hydrochloric acid, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a second residue. This second residue is purified by flash column chromatography (silica gel, hexane/ethyl acetate 4:1 v/v) to give (S)-3-t-butyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide (460 mg, 20%) as colorless crystals, mp 92° C.
EXAMPLE 3 (R/S)-3-(2-Fluorophenyl)isothiazole-5-carboxylic acid (1-thien-2-ylethyl)amide
(a) 5-(2-Fluorophenyl) 1,3,4!oxathiazolin-2-one
Chlorocarbonyl sulfenyl chloride (11.24 g, 86 mmol) is added dropwise to a stirred suspension of 2-fluorobenzamide (10.80 g, 78 mmol) in dry toluene. The mixture is heated gradually over a period of 30 minutes to a temperature of about 80° C. (a clear solution is formed with evolution of gas), stirred for approximately 1 h at 80° C., heated to about 98° C., stirred at 98° C. for 5 h, and distilled to remove the toluene and excess chlorocarbonyl sulfenyl chloride. The resultant pot residue is redissolved in toluene, washed sequentially with water, 5% sodium bicarbonate and water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a residue. This residue is recrystallized from petroleum ether to give 5-(2-fluorophenyl) 1,3,4!oxathiazolin-2-one (13.2 g, 86%) as off-white crystals, mp 50° C.
(b) Ethyl 3-(2-fluorophenyl)isothiazole-5-carboxylate
A solution of 5-(2-fluorophenyl) 1,3,4!oxathiazolin-2-one (1.97 g, 10 mmol) and ethyl propiolate (1.96 g, 20 mmol) in p-xylene is heated at reflux temperature for 48 h, treated with a further portion of ethyl propionate, heated at reflux temperature for another 48 h, and distilled to remove the solvent. The resultant residue is purified by flash column chromatography (silica gel, toluene) to give ethyl 3-(2-fluorophenyl)isothiazole-5-carboxylate (1.0 g, 40%) as yellow crystals, mp 53°-54° C., plus ethyl 3-(2-fluorophenyl)isothiazole-4-carboxylate (0.8 g, 32%) as a yellow oil.
(c) 3-(2-Fluorophenyl)isothiazole-5-carboxylic acid
A solution of sodium hydroxide (0.17 g, 4.2 mmol) in water (4 mL) is added to a stirred solution of ethyl 3-(2-fluorophenyl)isothiazole-5-carboxylate (0.88 g, 3.5 mmol) in ethanol. The mixture is stirred for 6 h at 50° C. The ethanol is then removed by distillation and the resulting aqueous phase is washed with diethyl ether, acidified with 2N hydrochloric acid and filtered. The filtercake is dried in vacuo to give 3-(2-fluorophenyl)isothiazole-5-carboxylic acid (0.67 g, 86%) as beige crystals, mp 191°-192° C.
(d) (R/S)-3-(2-Fluorophenyl)isothiazole-5-carboxylic acid (1-thien-2-ylethyl)amide
A stirred solution of 3-(2-fluorophenyl)isothiazole-5-carboxylic acid (0.67 g, 3.0 mmol) in dry tetrahydrofuran is treated with 1,1'-carbonyldiimidazole (CDI) (0.54 g, 3.3 mmol), heated at reflux temperature for 30 minutes, cooled to room temperature, treated with (R/S)-1-(thien-2-ylethyl)amine (0.57 g, 4.5 mmol), stirred for 10 minutes, treated with a solution of 1,8-diazabicyclo 5.4.0!undec-7-ene (DBU) (0.50 g, 3.3 mmol) in ethanol, heated at reflux temperature for 4.5 h, allowed to stand at room temperature overnight and distilled to remove the tetrahydrofuran. The distillation residue is dissolved in ethyl acetate, washed sequentially with 2N hydrochloric acid and water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a residue. This residue is recrystallized from toluene to yield (R/S)-3-(2-fluorophenyl)isothiazole-5-carboxylic acid (1-thien-2-ylethyl)amide (0.70 g, 70%) as beige crystals, mp 158°-159° C.
EXAMPLES 4-26
Using essentially the same procedures described in Examples 1-3 hereinabove, the following compounds are obtained and shown in Table I.
                                  TABLE I                                 
__________________________________________________________________________
 ##STR7##                                                                 
Ex. No                                                                    
    W        Y  R.sub.1                                                   
                     R.sub.2 R.sub.3                                      
                                Stereochem.                               
                                       MP(°C.)                     
__________________________________________________________________________
4   t-Butyl  H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)  94-96                              
5   Phenyl   H  H    Phenyl  CH.sub.3                                     
                                (S)    173-175                            
6   Phenyl   H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)  138-140                            
7   Styryl   H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
8   Cyclohexyl                                                            
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
9   Dimethylamino                                                         
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
10  2-Pyridyl                                                             
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
11  2-Thienyl                                                             
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
12  p-Tolyl  H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
13  4-Methoxyphenyl                                                       
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
14  2,4-Difluoro-                                                         
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)  109-110                            
    phenyl                                                                
15  Benzyl   H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
16  t-Butyl  Cl H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
17  t-Butyl  CH.sub.3                                                     
                H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
18  t-Butyl  H  CH.sub.3                                                  
                     2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
19  t-Butyl  H  CH.sub.3 CO                                               
                     2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
20  t-Butyl  H  H    2-Thienyl                                            
                             H  (R/S)                                     
21  t-Butyl  H  H    4-Chlorophenyl                                       
                             CH.sub.3                                     
                                (R/S)                                     
22  t-Butyl  H  H    p-Tolyl CH.sub.3                                     
                                (R/S)                                     
23  t-Butyl  H  H    2-Furyl CH.sub.3                                     
                                (R/S)                                     
24  t-Butyl  H  H    2-Pyridyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
25  t-Butyl  H  H    3-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)                                     
26  t-Butyl  H  H    2-Benzothienyl                                       
                             CH.sub.3                                     
                                (R/S)  121-122                            
27  4-Fluorophenyl                                                        
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)  138                                
28  4-Fluorophenyl                                                        
             H  H    Phenyl  CH.sub.3                                     
                                (S)    169                                
29  2,4-Difluoro-                                                         
             H  H    Phenyl  CH.sub.3                                     
                                (S)    140                                
    phenyl                                                                
30  4-Chlorophenyl                                                        
             H  H    Phenyl  CH.sub.3                                     
                                (S)    195                                
31  4-Chlorophenyl                                                        
             H  H    2-Thienyl                                            
                             CH.sub.3                                     
                                (R/S)  156                                
__________________________________________________________________________
EXAMPLE 32
Evaluation of the herbicidal activity of compounds of formula I
PLANT SPECIES USED
TRZAW Triticum aestivum
HORVW Hordeum vulgare
ZEAMX Zea mays
GOSHI Gossypium hirsutum
GLXMA Glycine max
ALOMY Alopecurus myosuroides
SETVI Setaria viridis
GALAP Galium aparine
STEME Stellaria media
VERPE Veronica persica
IPOHE Ipomoea hederacea
LAMPU Lamium purpureum
PAPRH Papaver rhoeas
MATIN Matricaria inodora
AMARE Amaranthus retroflexus
ABUTH Abutilon theophrasti
AMBEL Ambrosia artemisifolia
CHEAL Chenopodium album
The preemergence tests are conducted by spraying a liquid formulation of the test compound onto the soil in which the seeds of the plant species have recently been sown. The postemergence tests are conducted by spraying a liquid formulation of the test compound onto seedling plants.
The soil used in the tests is a prepared horticultural loam.
The formulations used in the tests are prepared from solutions of the test compound in acetone containing 0.4% by weight of an alkylphenol/ethylene oxide condensate. These acetone solutions are diluted with water and the resulting formulations applied at dosage levels corresponding to 0.8 kg of active material per hectare in a volume equivalent to 900 liters per hectare.
In the preemergence tests untreated sown soil, and in the postemergence tests untreated soil bearing seedling plants, are used as controls.
The herbicidal effect of the test compounds is evaluated twenty days after treatment and is recorded on a 0-9 scale. A rating of 0 indicates growth equivalent to the untreated control, a rating of 9 indicates complete death.
The results of the tests are shown in Table II below. An asterisk denotes the specified plant species was not treated in the test.
                                  TABLE II                                
__________________________________________________________________________
Herbicidal Evaluation of Test Compounds at 0.8 kg/ha                      
__________________________________________________________________________
Ex.                                                                       
   Appl.                                                                  
No.                                                                       
   Time                                                                   
       TRZAW                                                              
            HORVW                                                         
                 ZEAMX                                                    
                      GOSHI                                               
                          GLXHA                                           
                               ALOMY                                      
                                    SETVI                                 
                                         GALAP                            
                                              STEME                       
__________________________________________________________________________
1  pre 0    0    2    0   *    7    8    6    9                           
   post                                                                   
       4    5    2    8   8    5    9    9    9                           
2  pre *    *    *    *   *    *    *    *    *                           
   post                                                                   
       3    6    0    9   9    9    9    3    9                           
3  pre 0    0    0    0   0    0    0    0    0                           
   post                                                                   
       0    0    *    2   2    0    0    3    4                           
4  pre 0    0    2    0   2    5    8    0    9                           
   post                                                                   
       4    5    5    9   9    7    9    8    9                           
5  pre 0    0    0    0   0    0    0    0    1                           
   post                                                                   
       0    0    0    4   0    0    0    0    4                           
6  pre 0    0    0    0   0    0    0    0    4                           
   post                                                                   
       0    0    3    5   4    3    9    5    9                           
__________________________________________________________________________
Ex.                                                                       
   Appl.                                                                  
No.                                                                       
   Time                                                                   
       VERPE                                                              
            IPOHE                                                         
                 LAMPU                                                    
                      PAPRH                                               
                          MATIN                                           
                               AMARE                                      
                                    ABUTH                                 
                                         AMBEL                            
                                              CHEAL                       
__________________________________________________________________________
1  pre 9    3    8    9   9    9    9    8    8                           
   post                                                                   
       9    9    9    9   9    9    9    8    8                           
2  pre *    *    *    *   *    *    *    *    *                           
   post                                                                   
       9    9    5    9   9    *    9    8    9                           
3  pre 0    0    0    *   0    7    0    0    0                           
   post                                                                   
       0    2    3    5   2    4    3    1    6                           
4  pre 9    1    6    9   9    7    9    8    8                           
   post                                                                   
       9    9    6    9   9    7    9    8    9                           
5  pre 6    0    0    9   4    4    0    0    4                           
   post                                                                   
       0    0    3    4   0    6    4    0    2                           
6  pre 4    0    4    9   5    7    0    0    3                           
   post                                                                   
       7    6    4    7   5    9    8    6    7                           
__________________________________________________________________________

Claims (20)

I claim:
1. A compound of formula I ##STR8## wherein W represents an optionally substituted alkyl, alkenyl, cycloalkyl, dialkylamino, aryl, heteroaryl or aralkyl group;
Y represents a hydrogen atom; a halogen atom, or an optionally substituted alkyl group;
R1 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted acyl group;
Z represents an C1-4 alkylene group being optionally substiuted by a group selected from halogen atoms, and phenyl, nitro, hydroxyl, C1-4 alkoxy, C1-4 alkyl, C1-4 haloalkoxy, (C1-4 alkoxy) carbonyl groups, amino, alkyl- and phenyl-sulphinyl, -sulphenyl and -sulphonyl groups, and mono- or di(C1-4 alkyl) amino groups; and
R2 represents an aryl or heteroaryl group being optionally substituted by a group selected from halogen atoms, and nitro, cyano, amino, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and C1-4 haloalkoxy groups;
with the proviso that when Z represents an unsubstituted methylene group, then R2 does not represent an unsubstituted phenyl group; or
the N-oxides thereof; or
the optical isomers thereof.
2. The compound according to claim 1, wherein W represents an optionally substituted alkyl alkenyl, cycloalkyl, dialkylamino, phenyl, pyridyl, furyl or thienyl group.
3. The compound according to claim 1 wherein W represents a branched C3 -C6 alkyl group or a phenyl group optionally substituted with one or two substituents independently selected from halogen, C1 -C4 alkyl, C1 -C4 alkoxy and C1 -C4 haloalkyl.
4. The compound according to claim 1 wherein Y represents a hydrogen atom.
5. The compound according to claim 1 wherein R1 represents a hydrogen atom.
6. The compound according to claim 1 wherein Z represents --CH(R3)--; and R3 represents a hydrogen atom or an optionally substituted C1 -C2 alkyl group.
7. The compound according to claim 1 wherein R2 represents furyl, pyridyl, thienyl, benzothienyl, or phenyl optionally substituted by one or two substituents independently selected from halogen and C1 -C4 alkyl.
8. The compound according to claim 1 wherein W represents t-butyl or phenyl; Z represents --CH(CH3)--; and R2 represents phenyl or thienyl.
9. The compound according to claim 1 wherein the optically active isomer is the (S)-isomer.
10. The compound according to claim 1 selected from the group consisting of
(S)-3-t-butyl-isoxazole-5-carboxylic acid (1-phenylethyl)amide;
(S)-3-t-butyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(S)-3-phenyl-isoxazole-5-carboxylic acid (1-phenylethyl)amide;
(R/S)-3-phenyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-styryl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-cyclohexyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-dimethylamino-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(2'-pyridyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(2'-thienyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(4'-methylphenyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(4'-methoxyphenyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-(2',4'-difluorophenyl)isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-benzyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-butyl-4-chloro-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-butyl-4-methyl-isoxazole-5-carboxylic acid (1-thien-2-ylethyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid N-methyl,N-(1-thien-2-ylethyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid N-acetyl,N-(1-thien-2-ylethyl)amide;
3-t-butyl-isoxazole-5-carboxylic acid (thien-2-yl-methyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid (1-(4'-chlorophenyl)ethyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid (1-(4'-methylphenyl)ethyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid (1-furan-2-ylethyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid (1-(2'-pyridyl)ethyl)amide;
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid (1-thien-3-ylethyl)amide; and
(R/S)-3-t-butyl-isoxazole-5-carboxylic acid (1-(2'-benzothienyl)ethyl)amide.
11. A method for the control of undesirable monocotyledenous and dicotyledenous annual, perennial and aquatic plant species which comprises applying to the foliage of the plants or to the soil or water containing seeds or other propagating organs thereof a herbicidally effective amount of a compound of formula I ##STR9## wherein X represents an oxygen atom; W represents an optionally substituted alkyl, alkenyl, cycloalkyl, dialkylamino, aryl, heteroaryl or aralkyl group;
Y represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group;
R1 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted acyl group;
Z represents an optionally substituted C1 -C4 alkylene group; and
R2 represents an optionally substituted aryl or heteroaryl group; as defined in claim 1 or
the N-oxides thereof; or
the optical isomers thereof.
12. The method according to claim 11 having a formula I compound wherein W represents an optionally substituted alkyl, alkenyl, cycloalkyl, dialkylamino, phenyl, pyridyl, furyl or thienyl group; Y represents a hydrogen atom; Z represents a --CH(R3)-- group; and R3 represents a hydrogen atom or an optionally substituted C1 -C2 alkyl group.
13. The method according to claim 11 wherein said undesirable plant species are controlled in the presence of a crop.
14. The method according to claim 13 wherein the crop is a cereal crop or a leguminous crop.
15. The method according to claim 14 wherein the crop is wheat, barley, oat or corn.
16. The method according to claim 11 wherein the formula I compound is applied at a rate of about 0.01 kg/ha to 10 kg/ha.
17. A herbicidal composition which comprises a solid or liquid carrier and a herbicidally effective amount of a compound of formula I ##STR10## wherein W, X, Y, Z, R1 and R2 are as defined in claim 11.
18. The herbicidal composition according to claim 17 which comprises at least two carriers at least one of which is a surface-active agent.
19. The herbicidal composition according to claim 17 having a formula I compound wherein W represents an optionally substituted alkyl, alkenyl, cycloalkyl, dialkylamino, phenyl, pyridyl, furyl or thienyl group; Y represents a hydrogen atom; Z represents a --CH(R3)-- group; and R3 represents a hydrogen atom or an optionally substituted C1 -C2 alkyl group.
20. A process for the preparation of a compound of formula I which comprises reacting a compound of formula II ##STR11## wherein W, X and Y are as defined in claim 11 and L represents a leaving group, with a compound of formula III or IV ##STR12## wherein Z, R1 and R2 are as defined in claim 11 and B- is an anion.
US08/702,779 1995-08-24 1996-08-23 Herbicidal isoxazole and isothiazole-5-carboxamides Expired - Lifetime US5780393A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US08/702,779 US5780393A (en) 1995-08-24 1996-08-23 Herbicidal isoxazole and isothiazole-5-carboxamides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US272895P 1995-08-24 1995-08-24
US08/702,779 US5780393A (en) 1995-08-24 1996-08-23 Herbicidal isoxazole and isothiazole-5-carboxamides

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US08/342,579 Division US5726357A (en) 1993-06-07 1994-11-21 Flow sensor

Publications (1)

Publication Number Publication Date
US5780393A true US5780393A (en) 1998-07-14

Family

ID=21702199

Family Applications (1)

Application Number Title Priority Date Filing Date
US08/702,779 Expired - Lifetime US5780393A (en) 1995-08-24 1996-08-23 Herbicidal isoxazole and isothiazole-5-carboxamides

Country Status (6)

Country Link
US (1) US5780393A (en)
EP (1) EP0761654B1 (en)
AR (1) AR003340A1 (en)
AT (1) ATE243204T1 (en)
BR (1) BR9603513A (en)
DE (1) DE69628705T2 (en)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000020358A2 (en) * 1998-08-20 2000-04-13 Agouron Pharmaceuticals, Inc. NON-PEPTIDE GnRH AGENTS, METHODS AND INTERMEDIATES FOR THEIR PREPARATION
US20040010033A1 (en) * 2001-02-20 2004-01-15 Pfizer Inc. Non-peptide GnRH agents, methods and intermediates for their preparation
US20050222151A1 (en) * 2004-03-31 2005-10-06 Carruthers Nicholas I Non-Imidazole heterocyclic compounds
US7101878B1 (en) 1998-08-20 2006-09-05 Agouron Pharmaceuticals, Inc. Non-peptide GNRH agents, methods and intermediates for their preparation
US20070281923A1 (en) * 2006-05-30 2007-12-06 Keith John M Substituted pyridyl amide compounds as modulators of the histamine h3 receptor
US20080045507A1 (en) * 2006-06-29 2008-02-21 Allison Brett D Substituted benzamide modulators of the histamine h3 receptor
US8883776B2 (en) 2007-11-20 2014-11-11 Janssen Pharmaceutica N.V. Cycloalkyloxy- and heterocycloalkyloxypyridine compounds as modulators of the histamine H3 receptor
WO2016102420A3 (en) * 2014-12-22 2016-09-01 Bayer Cropscience Aktiengesellschaft Novel isothiazolamides, processes for their preparation and their use as herbicides and/or plant growth regulators
WO2016105485A3 (en) * 2014-12-23 2016-09-01 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing cftr activity
WO2016102435A3 (en) * 2014-12-22 2016-09-09 Bayer Cropscience Aktiengesellschaft Novel isothiazolamides, processes for their preparation and their use as fungicides
US9745292B2 (en) 2014-03-13 2017-08-29 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US9790219B2 (en) 2014-03-13 2017-10-17 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US10174014B2 (en) 2014-06-19 2019-01-08 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US10344023B2 (en) 2014-12-23 2019-07-09 Proteostasis Therapeutics, Inc. Derivatives of 3-heteroarylisoxazol-5-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10392378B2 (en) 2014-12-23 2019-08-27 Proteostasis Therapeutics, Inc. Derivatives of 5-phenyl- or 5-heteroarylathiazol-2-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10550106B2 (en) 2015-10-06 2020-02-04 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for modulating CFTR
US10548878B2 (en) 2015-07-24 2020-02-04 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods of increasing CFTR activity
US10662207B2 (en) 2016-04-07 2020-05-26 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for modulating CFTR
US10738011B2 (en) 2014-12-23 2020-08-11 Proteostasis Therapeutics, Inc. Derivatives of 5-(hetero)arylpyrazol-3-carboxylic amide or 1-(hetero)aryltriazol-4-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10899751B2 (en) 2016-06-21 2021-01-26 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2255294T3 (en) 1998-08-07 2006-06-16 Chiron Corporation ISOXAZOL DERIVATIVES REPLACED AS MODULATORS OF THE STROGEN RECEPTOR.
WO2003074501A1 (en) * 2002-03-07 2003-09-12 Sds Biotech K.K. Substituted isoxazole alkylamine derivative and agri- and horticultural fungicide
WO2017207395A1 (en) 2016-06-02 2017-12-07 Bayer Cropscience Aktiengesellschaft Isothiazolopyridones, processes for their preparation and their use as fungicides
US20200317690A1 (en) 2016-06-02 2020-10-08 Bayer Cropscience Aktiengesellschaft Novel isothiazolopyridones, processes for their preparation and their use as herbicides and/or plant growth regulators

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3668215A (en) * 1967-11-25 1972-06-06 Bayer Ag Aryl-sulphonyl-semicarbazides containing heterocyclic acylamino groups
US3912756A (en) * 1973-04-21 1975-10-14 Boehringer Mannheim Gmbh New phenoxyalkyl-carboxylic acid compounds and therapeutic compositions
JPS5444686A (en) * 1977-09-09 1979-04-09 Taiho Pharmaceutical Co Ltd Sstriazine derivative and its manufacture
DE3618004A1 (en) * 1986-05-28 1987-12-03 Bayer Ag Use of amides for improving the crop plant tolerance of herbicidally active sulphonyliso(thio)urea derivatives
EP0313091A2 (en) * 1987-10-23 1989-04-26 MITSUI TOATSU CHEMICALS, Inc. Amide derivatives, processes for production thereof, and agricultural-horticultural fungicide containing them
EP0428434A2 (en) * 1989-11-06 1991-05-22 Sanofi Compounds of aromatic amines and their enantiomers, process for their preparation and pharmaceutical compositions containing them
US5039694A (en) * 1986-11-06 1991-08-13 Nissan Chemical Industries, Ltd. Substituted-amido compounds and phytopathogenic fungicides containing the same
US5080708A (en) * 1988-04-13 1992-01-14 Basf Aktiengesellschaft Isoxazole(isothiazole)-5-carboxamides
DE4108183A1 (en) * 1991-03-14 1992-09-17 Basf Ag ISOXAZOL AND ISOTHIAZOL 5-CARBON ACID AMIDE
US5201932A (en) * 1989-09-22 1993-04-13 Basf Aktiengesellschaft Carboxamides
US5240951A (en) * 1990-09-20 1993-08-31 Mitsui Toatsu Chemicals, Incorporated Isothiazolecarboxylic acid derivatives, rice blast control agents containing the same as active ingredients, and rice blast control method applying the control agents
GB2284600A (en) * 1994-01-21 1995-06-14 Shell Int Research Herbicidal 3-(hetero)aryl-4-acylisoxazole compositions and compounds
EP0669326A1 (en) * 1994-02-25 1995-08-30 BASF Aktiengesellschaft Cyanoisoxazoles

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0418667B1 (en) * 1989-09-22 1995-08-16 BASF Aktiengesellschaft Carboxylic acid amides

Patent Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3755587A (en) * 1967-11-25 1973-08-28 Bayer Ag Compositions and methods for lowering blood sugar using aryl sulphonylsemicarbazides containing heterocyclic acylamino groups
US3668215A (en) * 1967-11-25 1972-06-06 Bayer Ag Aryl-sulphonyl-semicarbazides containing heterocyclic acylamino groups
US3912756A (en) * 1973-04-21 1975-10-14 Boehringer Mannheim Gmbh New phenoxyalkyl-carboxylic acid compounds and therapeutic compositions
JPS5444686A (en) * 1977-09-09 1979-04-09 Taiho Pharmaceutical Co Ltd Sstriazine derivative and its manufacture
DE3618004A1 (en) * 1986-05-28 1987-12-03 Bayer Ag Use of amides for improving the crop plant tolerance of herbicidally active sulphonyliso(thio)urea derivatives
US5039694A (en) * 1986-11-06 1991-08-13 Nissan Chemical Industries, Ltd. Substituted-amido compounds and phytopathogenic fungicides containing the same
EP0313091A2 (en) * 1987-10-23 1989-04-26 MITSUI TOATSU CHEMICALS, Inc. Amide derivatives, processes for production thereof, and agricultural-horticultural fungicide containing them
US5080708A (en) * 1988-04-13 1992-01-14 Basf Aktiengesellschaft Isoxazole(isothiazole)-5-carboxamides
US5201932A (en) * 1989-09-22 1993-04-13 Basf Aktiengesellschaft Carboxamides
EP0428434A2 (en) * 1989-11-06 1991-05-22 Sanofi Compounds of aromatic amines and their enantiomers, process for their preparation and pharmaceutical compositions containing them
US5240951A (en) * 1990-09-20 1993-08-31 Mitsui Toatsu Chemicals, Incorporated Isothiazolecarboxylic acid derivatives, rice blast control agents containing the same as active ingredients, and rice blast control method applying the control agents
DE4108183A1 (en) * 1991-03-14 1992-09-17 Basf Ag ISOXAZOL AND ISOTHIAZOL 5-CARBON ACID AMIDE
GB2284600A (en) * 1994-01-21 1995-06-14 Shell Int Research Herbicidal 3-(hetero)aryl-4-acylisoxazole compositions and compounds
EP0669326A1 (en) * 1994-02-25 1995-08-30 BASF Aktiengesellschaft Cyanoisoxazoles

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
Chem. Abstr. 132705e, vol. 72, No. 25 (1970) & JP-B1-45 007 054 (SHIONOGI AND CO., LTD.) 11 March 1970 *
Chem. Abstr. 132705e, vol. 72, No. 25 (1970).
Chem. Abstr. 175401n, vol. 91, No. 21 (1979) & JP-A-54 044 686 (TAIHO YAKUHIN KOGYO K.K.) 9 April 1979 *
Chem. Abstr. 175401n, vol. 91, No. 21 (1979).
Musant C. Fabrini L. Gazetta Chimica Italiana, vol. 81, pp. 117 124 (1951). *
Musant C. Fabrini L. Gazetta Chimica Italiana, vol. 81, pp. 117-124 (1951).
Plumpe, H, Arzneimittel Forschung, vol. 24, No. 3A, pp. 363 374 (1974). *
Plumpe, H, Arzneimittel--Forschung, vol. 24, No. 3A, pp. 363-374 (1974).

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7101878B1 (en) 1998-08-20 2006-09-05 Agouron Pharmaceuticals, Inc. Non-peptide GNRH agents, methods and intermediates for their preparation
WO2000020358A3 (en) * 1998-08-20 2000-11-16 Agouron Pharma NON-PEPTIDE GnRH AGENTS, METHODS AND INTERMEDIATES FOR THEIR PREPARATION
WO2000020358A2 (en) * 1998-08-20 2000-04-13 Agouron Pharmaceuticals, Inc. NON-PEPTIDE GnRH AGENTS, METHODS AND INTERMEDIATES FOR THEIR PREPARATION
US20040010033A1 (en) * 2001-02-20 2004-01-15 Pfizer Inc. Non-peptide GnRH agents, methods and intermediates for their preparation
US20080306066A1 (en) * 2004-03-31 2008-12-11 Carruthers Nicholas I Non-imidazole heterocyclic compounds
US7947718B2 (en) 2004-03-31 2011-05-24 Janssen Pharmaceutica Nv Isoxazole compounds as histamine H3 modulators
WO2005097751A2 (en) * 2004-03-31 2005-10-20 Janssen Pharmaceutica, N.V. Non-imidazole heterocyclic compounds as histamine h3-receptor ligands
US20050222151A1 (en) * 2004-03-31 2005-10-06 Carruthers Nicholas I Non-Imidazole heterocyclic compounds
WO2005097751A3 (en) * 2004-03-31 2006-03-09 Janssen Pharmaceutica Nv Non-imidazole heterocyclic compounds as histamine h3-receptor ligands
US7423147B2 (en) 2004-03-31 2008-09-09 Janssen Pharmaceutical, N.V. Pyridine compounds as histamine H3 modulators
US20100022539A1 (en) * 2004-03-31 2010-01-28 Carruthers Nicholas I Isoxazole Compounds as Histamine H3 modulators
US7777031B2 (en) 2006-05-30 2010-08-17 Janssen Pharmaceutica Nv Substituted pyridyl amide compounds as modulators of the histamine H3 receptor
US8637520B2 (en) 2006-05-30 2014-01-28 Janssen Pharmaceutica Nv Substituted pyridyl amide compounds as modulators of the histamine H3 receptor
US8940731B2 (en) 2006-05-30 2015-01-27 Janssen Pharmaceutica Nv Substituted pyridyl amide compounds as modulators of the histamine H3 receptor
US9321729B2 (en) 2006-05-30 2016-04-26 Janssen Pharmaceutica Nv Substituted pyridyl amide compounds as modulators of the histamine H3 receptor
US20070281923A1 (en) * 2006-05-30 2007-12-06 Keith John M Substituted pyridyl amide compounds as modulators of the histamine h3 receptor
US20080045507A1 (en) * 2006-06-29 2008-02-21 Allison Brett D Substituted benzamide modulators of the histamine h3 receptor
US8883776B2 (en) 2007-11-20 2014-11-11 Janssen Pharmaceutica N.V. Cycloalkyloxy- and heterocycloalkyloxypyridine compounds as modulators of the histamine H3 receptor
US9790219B2 (en) 2014-03-13 2017-10-17 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US9745292B2 (en) 2014-03-13 2017-08-29 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US10017503B2 (en) 2014-03-13 2018-07-10 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US10738040B2 (en) 2014-06-19 2020-08-11 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US10174014B2 (en) 2014-06-19 2019-01-08 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
WO2016102435A3 (en) * 2014-12-22 2016-09-09 Bayer Cropscience Aktiengesellschaft Novel isothiazolamides, processes for their preparation and their use as fungicides
WO2016102420A3 (en) * 2014-12-22 2016-09-01 Bayer Cropscience Aktiengesellschaft Novel isothiazolamides, processes for their preparation and their use as herbicides and/or plant growth regulators
JP2018501252A (en) * 2014-12-22 2018-01-18 バイエル・クロップサイエンス・アクチェンゲゼルシャフト Novel isothiazole amides, methods for their preparation and their use as herbicides and / or plant growth regulators
CN107249329A (en) * 2014-12-22 2017-10-13 拜耳作物科学股份公司 New isothiazole acid amides, its preparation method and its purposes as herbicide and/or plant growth regulator
CN107207487A (en) * 2014-12-23 2017-09-26 蛋白质平衡治疗股份有限公司 Compound, composition and method for improving CFTR activity
WO2016105485A3 (en) * 2014-12-23 2016-09-01 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing cftr activity
US10344023B2 (en) 2014-12-23 2019-07-09 Proteostasis Therapeutics, Inc. Derivatives of 3-heteroarylisoxazol-5-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10392378B2 (en) 2014-12-23 2019-08-27 Proteostasis Therapeutics, Inc. Derivatives of 5-phenyl- or 5-heteroarylathiazol-2-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10392372B2 (en) 2014-12-23 2019-08-27 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
CN107207487B (en) * 2014-12-23 2021-12-28 蛋白质平衡治疗股份有限公司 Compounds, compositions and methods for increasing CFTR activity
US11098035B2 (en) 2014-12-23 2021-08-24 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
US10738011B2 (en) 2014-12-23 2020-08-11 Proteostasis Therapeutics, Inc. Derivatives of 5-(hetero)arylpyrazol-3-carboxylic amide or 1-(hetero)aryltriazol-4-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10548878B2 (en) 2015-07-24 2020-02-04 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods of increasing CFTR activity
US11083709B2 (en) 2015-07-24 2021-08-10 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods of increasing CFTR activity
US11136313B2 (en) 2015-10-06 2021-10-05 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for modulating CFTR
US10550106B2 (en) 2015-10-06 2020-02-04 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for modulating CFTR
US10662207B2 (en) 2016-04-07 2020-05-26 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for modulating CFTR
US11248010B2 (en) 2016-04-07 2022-02-15 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for modulating CFTR
US10899751B2 (en) 2016-06-21 2021-01-26 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity

Also Published As

Publication number Publication date
EP0761654B1 (en) 2003-06-18
EP0761654A1 (en) 1997-03-12
BR9603513A (en) 1998-05-12
DE69628705D1 (en) 2003-07-24
AR003340A1 (en) 1998-07-08
ATE243204T1 (en) 2003-07-15
DE69628705T2 (en) 2004-05-13

Similar Documents

Publication Publication Date Title
US5780393A (en) Herbicidal isoxazole and isothiazole-5-carboxamides
US5089043A (en) Heterocyclic oxy-phenoxyacetic acid derivatives and their use as herbicides
JP4936623B2 (en) Fungicide
JPH01121287A (en) Imidazolines and insecticide
US4230481A (en) Pyrazole derivatives useful as a herbicidal component
JP3557230B2 (en) New herbicides
US20020082267A1 (en) Fungicidal phenylamidine derivatives
US5178663A (en) 3-alkoxyalkanoic acid derivative, process for preparing the same and herbicide using the same
JPH0356466A (en) Pyridazinones having insecticide and tickicide activity
US4792565A (en) Pyrazolecarbonylamine derivatives and agricultural and horticultural fungicides containing said compounds
KR20060031612A (en) Use of isoindolinone derivatives as insecticides
US4885023A (en) Thiadiazabicyclononane derivatives and herbicidal compositions
CN108341808B (en) Oxadiazole pyrazole compound and application thereof
JP3103197B2 (en) Herbicidal compounds
US5591695A (en) Herbicidal [1,3,4]oxadiazoles and thiadiazoles
JP2690816B2 (en) Quinolinyl oxadiazole herbicide
US5486521A (en) Pyrimidinyl aryl ketone oximes
US5090994A (en) Heterocyclic compounds and herbicidal compositions containing the compounds as effective components
US5583092A (en) Herbicidal [1,2,4] thiadiazoles
EP0726263A2 (en) Herbicidal (1,3,4)oxadiazoles and thiadiazoles
US5110348A (en) Glycine compounds and herbicidal compositions thereof
US5017213A (en) 1-phenylpyrroles
JP2004231528A (en) Amide derivative
US5525580A (en) Substituted benzoyl cyclic enone, process for preparation, and herbicide
WO1998004525A1 (en) Fungicidal n-aryl five-membered cyclic imides

Legal Events

Date Code Title Description
AS Assignment

Owner name: AMERICAN HOME PRODUCTS CORPORATION, NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:NEWTON, TREVOR W.;REEL/FRAME:008244/0830

Effective date: 19960827

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

STCF Information on status: patent grant

Free format text: PATENTED CASE

CC Certificate of correction
AS Assignment

Owner name: BASF AKTIENGESELLSCHAFT, NORTH CAROLINA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:AMERICAN CYANAMID COMPANY;REEL/FRAME:012276/0001

Effective date: 20011017

FPAY Fee payment

Year of fee payment: 4

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12